1. Field of the Invention
This invention relates to potency stabilized tocopherol in a dry, particulate, free-flowing form. The stabilized products are in the form of powders or fine granules in which a carrier supports the tocopherol, whose potency is stabilized with certain acid compounds.
2. Statement of Related Art
Vitamin E comprises a group of natural substances known as tocopherols. These are fat soluble, closely related chemical compounds found in vegetable oils such as wheat germ oil, soy bean oil and the like. Alpha-tocopherol has the greatest biological activity while its homologs have Vitamin E activity to a lesser extent. The tocopherols and their esters are normally water insoluble, oily, waxy or low-melting, which properties generally make them unsuitable for certain pharmaceutical applications, particularly those in which a powder is required such as in tablets or capsules.
In recent years, efforts have been to convert various vitamin products, including Vitamin E, to a free-flowing, high density agglomerated composition. Illustrative thereof are U.S. Pat. Nos. 3,914,430; 3,947,596; 3,959,472; and 3,962,384 assigned to Hoffman-La Roche, Inc., which are all based on U.S. patent application Ser. No. 242,789, filed Apr. 10, 1972 and now abandoned. In general, these patents disclose a spray drying process for preparing free-flowing, high density agglomerates which are suitable for compression into tablets. In these patents, hydrolyzed gelatin and/or other ultra-fine absorbents are employed as a carrier for the vitamin. In order to ensure the desired stability of Vitamin E activity in the final powder it is preferred to use the tocopherol esters.
In U.S. Pat. No. 3,608,083, also assigned to Hoffman-La Roche, there is disclosed another spray drying method for producing a Vitamin E powder with good pelleting characteristics for incorporation into tablets and capsules. The powders are composed of a Vitamin E active compound and carried by a gelatin hydrolysate having a molecular weight of about 9,000 to about 10,000 and a zero Bloom. In Example 3 a multi-vitamin tablet containing Vitamin C (ascorbic acid) and Vitamin A along with Vitamin E is formulated. The powders are prepared by a spray drying process.
U.S. Pat. No. 3,869,539, assigned to A/S Ferrosan, discloses a method of preparing a dry, particulate, free-flowing form dispersible in cold water of fat-soluble vitamins including Vitamin E. In this method, the vitamins are incorporated in a finely dispersed form in a mass of gelatin. In discussing prior methods of forming such products from gelatin, it is disclosed that the aqueous gelatin solutions must be initially treated with ascorbic acid or mixtures thereof with citric acid, or a mixture of citric acid and sorbose. This treatment method, however, is noted as suffering from various drawbacks and the invention disclosed in U.S. Pat. No. 3,869,539 is a method of avoiding such drawbacks through using a mass of gelatin partially decomposed with a base or an inorganic acid, which is then neutralized to a pH value between 4.5 and 7.
In a series of U.S. Pat. No. 4,395,422; 4,262,017; 4,486,435, assigned to B.A.S.F. Wyandotte Corporation, there is disclosed spray dried Vitamin E powders utilizing hydrolyzed gelatin and caseinates. The use of flow improvers, such as synthetic silica are also disclosed. In U.S. Pat. No. 4,486,435, hydrophobic silica is employed.
Mixtures of Vitamin E and certain acids have been studied for use as anti-oxidants to protect various materials such as lard and vegetable oils, fatty acids, sardines and arachidonic acid. These studies can be seen from the following literature:
(a) "Interaction of Galvinoxyl Radical with Ascorbic Acid, Cysteine, and Glutathione in Homogeneous Solution and in Aqueous Dispersions." J. Tsuchiya, T. Yamada, E. Niki, and Y. Kimiya, BULL. CHEM. SOC. JAPAN, 1985, 58(1), 326-30. PA0 (b) "Studies on the Activities of Natural Anti-oxidants (Part 3). Preventing Effects of Natural Anti-oxidants on Oxidation of Dried Sardine". K. Nishikawa, H. Oka, and T. Yasuda, KENYU-HOKOKU-EHIME-KEN KOGYO GIJUTSU 1984, 22, 15-20. PA0 (c) "Arachidonic Acid Anti-oxidation in an Aqueous Media Effect of .alpha.-tocopherol, Cysteine and Nucleic Acids". B. Bozin, J. Cillard, J. P. Kaskas, and P. Cillard, JAOCS, 1984, 61, 1212-1215. PA0 (d) "Some Effects of Amino Acids and Certain Other Substances on Lard Containing Phenolic Anti-oxidants". D. F. Clausen, W. O. Lundberg, and G. O. Burr, JAOCS, 1947, 24, 403-404.
In forming such dry, free-flowing Vitamin E compositions, however, a loss of potency has been recognized. It is important and desirable that the Vitamin E powders contain and maintain a high potency in use.